Search

Chrononutrition is a rapidly evolving field of nutritional epidemiology that addresses the complex relationship between temporal eating patterns, circadian rhythms, and metabolic health, but most prior research has focused on the cardiometabolic consequences of time-restricted feeding and intermittent fasting. The purpose of this topical review is to summarize epidemiological evidence from observational and intervention studies regarding the role of chrononutrition metrics related to eating timing and regularity in cardiometabolic health preservation and cardiovascular disease prevention. Observational studies are limited due to the lack of time-stamped diet data in most population-based studies. Findings from cohort studies generally indicate that breakfast skipping or the later timing of the first eating occasion, a later lunch and dinner, and a greater proportion of caloric intake consumed in the evening are associated with adverse cardiometabolic outcomes, including higher risk for coronary heart disease, hypertension, type 2 diabetes, obesity, dyslipidemia, and systemic inflammation. Randomized controlled trials are also limited, as most in the field of chrononutrition focus on the cardiometabolic consequences of time-restricted feeding. Overall, interventions that shift eating timing patterns to earlier in the day and that restrict evening caloric intake tend to have protective effects on cardiometabolic health, but small sample sizes and short follow-up are notable limitations. Innovation in dietary assessment approaches, to develop low-cost validated tools with acceptable participant burden that reliably capture chrononutrition metrics, is needed for advancing observational evidence. Culturally responsive pragmatic intervention studies with sufficiently large and representative samples are needed to understand the impact of fixed and earlier eating timing schedules on cardiometabolic health. Additional research is warranted to understand the modifiable determinants of temporal eating patterns, to investigate the role of chrononutrition in the context of other dimensions of diet (quantity, quality, and food and nutrition security) in achieving cardiometabolic health equity, and to elucidate underlying physiological mechanisms.

Abstract Background Especially in high HIV prevalence contexts, such as Zambia, effective biomedical prevention tools are needed for priority populations (PPs), including key populations (KPs), who are at higher risk. HIV pre-exposure prophylaxis (PrEP) has been scaled up nationally in Zambia, but little is known about barriers to PrEP use among specific PPs to date. Methods To understand barriers and facilitators to PrEP use in Zambia, we conducted a qualitative case study of PrEP services to PPs including sero-discordant couples (SDCs), female sex workers (FSWs), and men who have sex with men (MSM) in Livingstone. The study conducted in 2021 included in-depth interviews (n = 43) guided by the socio-ecological model, and focus group discussions (n = 4) with clinic and community-based providers and PrEP-eligible clients including users and non-users across PP groups. We used thematic analysis to analyze data using codes derived both deductively and inductively. Results We found multilevel barriers and facilitators to PrEP use. Cross-cutting barriers shared across PP groups included amplifying effects of PrEP being mistaken for antiretroviral drugs used to treat HIV, including anticipated stigma, and concerns about side-effects based on both misinformation and experience. In addition, stigmatized identities, particularly that of MSM, served as a barrier to PrEP use. The fear of being mislabeled as having HIV was of greatest concern for FSWs. Facilitators to PrEP use primarily included the importance of confidential, KP-sensitive services, and the role of informed, supportive family, friends, and peers. Participants across all PP groups urged expanded education efforts to increase awareness of PrEP within the general population toward mitigating concerns of being mislabeled as living with HIV. Conclusion To our knowledge, this is the first qualitative study of the PrEP cascade among multiple PPs in Zambia. This study provides important explanation for the low rates of PrEP continuation found in earlier demonstration trials among KPs in Zambia. The study also offers recommendations for programming efforts going forward such as inclusive PrEP awareness campaigns, expanded KP sensitivity training, and related efforts to thwart PrEP stigma while expanding access.

Introduction: Cardiac glycosides comprise medications such as digoxin and digitoxin, plants, and even certain toad venoms. Intoxication with cardiac glycosides can lead to hemodynamic instability and cardiac arrest. With this narrative review, our objective was to determine if any therapy used in a near-cardiac arrest state due to cardiac glycoside poisoning could improve survival with favourable functional and neurological outcomes. Methods: We searched the Medline, PubMed, EMBASE and Cochrane Library databases up to February 2022 for controlled trials, observational studies, and case reports. We reviewed studies if participants were exposed to a cardiac glycoside, had hemodynamic instability, and an intervention was attempted to reverse the toxicity. The effect of interventions on (1) survival with favourable functional and neurological outcomes and (2) correction of hemodynamic instability was assessed. Results: Of the 2422 studies found, 73 were included for analysis, of which 58 were case reports or series, and 15 were observational cohorts. Most patients were intoxicated with medication (60 individual cases and 11 observational cohorts). Administration of digoxin immune-Fab fragments was associated with improved hemodynamic status and survival in medication patients. Administration of magnesium, cardioversion, and cardiac pacing was associated with favourable outcomes, while administration of atropine, antiarrhythmics, or calcium was not. Conclusion: In patients with hemodynamic instability due to cardiac glycoside intoxication, digoxin immune-Fab fragments should be given, and magnesium administration, cardioversion, and cardiac pacing can reasonably be attempted.

IntroductionOperculo-insular epilepsy (OIE) is a rare condition amenable to surgery in well-selected cases. Despite the high rate of neurological complications associated with OIE surgery, most postoperative deficits recover fully and rapidly. We provide insights into this peculiar pattern of functional recovery by investigating the longitudinal reorganization of structural networks after surgery for OIE in 10 patients.MethodsStructural T1 and diffusion-weighted MRIs were performed before surgery (t0) and at 6 months (t1) and 12 months (t2) postoperatively. These images were processed with an original, comprehensive structural connectivity pipeline. Using our method, we performed comparisons between the t0 and t1 timepoints and between the t1 and t2 timepoints to characterize the progressive structural remodeling.ResultsWe found a widespread pattern of postoperative changes primarily in the surgical hemisphere, most of which consisted of reductions in connectivity strength (CS) and regional graph theoretic measures (rGTM) that reflect local connectivity. We also observed increases in CS and rGTMs predominantly in regions located near the resection cavity and in the contralateral healthy hemisphere. Finally, most structural changes arose in the first six months following surgery (i.e., between t0 and t1).DiscussionTo our knowledge, this study provides the first description of postoperative structural connectivity changes following surgery for OIE. The ipsilateral reductions in connectivity unveiled by our analysis may result from the reversal of seizure-related structural alterations following postoperative seizure control. Moreover, the strengthening of connections in peri-resection areas and in the contralateral hemisphere may be compatible with compensatory structural plasticity, a process that could contribute to the recovery of functions seen following operculo-insular resections for focal epilepsy.

BackgroundThe timing and regularity of eating patterns could play a role in systemic inflammation, as circadian clocks responsible for daily rhythms of inflammatory signaling are entrained by food intake.PurposeTo evaluate associations of intra-weekly and weekday-weekend differences in eating timing patterns with high-sensitivity C-reactive protein (hsCRP).MethodsA community-based sample of 103 U.S. women from the American Heart Association Go Red for Women Strategically Focused Research Network completed a meal-timing questionnaire and provided a blood sample for measurement of hsCRP. Differences in weekday versus weekend eating start time, eating end time, and nightly fasting duration were calculated as eating jetlag metrics. Intra-weekly variability in eating timing patterns was defined by the standard deviation (SD) of these variables. Multivariable linear regression models were used to evaluate cross-sectional associations of eating timing variability metrics with hsCRP.ResultsEach additional 30-min difference in weekday-weekend eating end time was related to 13% higher hsCRP (p = .023). Similarly, every 30-min increase in eating end time SD, reflecting greater variability in timing of last eating occasion, was associated with 29% higher hsCRP. Per 1-hr weekday-weekend difference in nightly fasting duration, there was a 45% elevation in hsCRP (p = .003). Every 30-min increase in nightly fasting duration SD, representing greater variability in span of the daily fasting/eating periods, was associated with 46% higher hsCRP.ConclusionsVariable eating timing patterns were associated with higher hsCRP. Intervention studies are needed to determine whether stabilizing the timing of eating occasions may represent a novel strategy to reduce chronic inflammation.

Patients with primary mitochondrial oxidative phosphorylation (OxPhos) defects present with fatigue and multi-system disorders, are often lean, and die prematurely, but the mechanistic basis for this clinical picture remains unclear. By integrating data from 17 cohorts of patients with mitochondrial diseases (n = 690) we find evidence that these disorders increase resting energy expenditure, a state termed hypermetabolism. We examine this phenomenon longitudinally in patient-derived fibroblasts from multiple donors. Genetically or pharmacologically disrupting OxPhos approximately doubles cellular energy expenditure. This cell-autonomous state of hypermetabolism occurs despite near-normal OxPhos coupling efficiency, excluding uncoupling as a general mechanism. Instead, hypermetabolism is associated with mitochondrial DNA instability, activation of the integrated stress response (ISR), and increased extracellular secretion of age-related cytokines and metabokines including GDF15. In parallel, OxPhos defects accelerate telomere erosion and epigenetic aging per cell division, consistent with evidence that excess energy expenditure accelerates biological aging. To explore potential mechanisms for these effects, we generate a longitudinal RNASeq and DNA methylation resource dataset, which reveals conserved, energetically demanding, genome-wide recalibrations. Taken together, these findings highlight the need to understand how OxPhos defects influence the energetic cost of living, and the link between hypermetabolism and aging in cells and patients with mitochondrial diseases.

Ultraviolet (UV)-reflectance is an essential signal of many plant species, which use wavelength-selective pigments in floral reproductive structures to determine the color of flowers and how they appear to their aerial pollinators, primarily bees. This paper presents a pollinator-inspired remote-sensing system incorporating UV reflectance into a flower detector for strawberry crops. We designed a compact, cost-effective UV-sensitive camera for aerial remote sensing over crop rows. Our camera and a deep-learning algorithm comprise our Nature-Inspired Detector (NID) system. We trained YOLOv5 and Faster R-CNN on our dataset of strawberry images incorporating the UV spectrum (300–400 nm). Our results showed that NID-based YOLO V5 outperformed NID-based Faster R-CNN in training time (0.3 vs. 4.5–5.5 hours) and mean Average Precision—mAP (0.951 vs. 0.934). We also present the field-test of our NID-based YOLOv5 system on a drone platform to validate its ability to detect strawberry flowers.

Validity as a social imperative foregrounds the social consequences of assessment and highlights the importance of building quality into the assessment development and monitoring processes. Validity as a social imperative is informed by current assessment trends such as programmatic-, longitudinal-, and rater-based assessment, and is one of the conceptualizations of validity currently at play in the Health Professions Education (HPE) literature. This Black Ice is intended to help readers to get a grip on how to embed principles of validity as a social imperative in the development and quality monitoring of an assessment. This piece draws on a program of work investigating validity as a social imperative, key HPE literature, and data generated through stakeholder interviews. We describe eight ways to implement validation practices that align with validity as a social imperative.

Background: Educators now use reported observations when assessing trainees’ performance. Unfortunately, they have little information about how to design and implement assessments based on reported observations. Objective: The purpose of this scoping review was to map the literature on the use of reported observations in judging health professions education (HPE) trainees' performances. Methods: Arksey and O'Malley’s (2005) method was used with four databases (sources: ERIC, CINAHL, MEDLINE, PsycINFO). Eligibility criteria for articles were: documents in English or French, including primary data, and initial or professional training; (2) training in an HPE program; (3) workplace-based assessment; and (4) assessment based on reported observations. The inclusion/exclusion, and data extraction steps were performed (agreement rate > 90%). We developed a data extraction grid to chart the data. Descriptive analyses were used to summarize quantitative data, and the authors conducted thematic analysis for qualitative data. Results: Based on 36 papers and 13 consultations, the team identified six steps characterizing trainee performance assessment based on reported observations in HPE: (1) making first contact, (2) observing and documenting the trainee performance, (3) collecting and completing assessment data, (4) aggregating assessment data, (5) inferring the level of competence, and (6) documenting and communicating the decision to the stakeholders. Discussion: The design and implementation of assessment based on reported observations is a first step towards a quality implementation by guiding educators and administrators responsible for graduating competent professionals. Future research might focus on understanding the context beyond assessor cognition to ensure the quality of meta-assessors’ decisions.

Abstract Background Hearing loss predicts cognitive decline and falls risk. It has been argued that degraded hearing makes listening effortful, causing competition for higher-level cognitive resources needed for secondary cognitive or motor tasks. Therefore, executive function training has the potential to improve cognitive performance, in turn improving mobility, especially when older adults with hearing loss are engaged in effortful listening. Moreover, research using mobile neuroimaging and ecologically valid measures of cognition and mobility in this population is limited. The objective of this research is to examine the effect of at-home cognitive training on dual-task performance using laboratory and simulated real-world conditions in normal-hearing adults and older hearing aid users. We hypothesize that executive function training will lead to greater improvements in cognitive-motor dual-task performance compared to a wait-list control group. We also hypothesize that executive function training will lead to the largest dual-task improvements in older hearing aid users, followed by normal-hearing older adults, and then middle-aged adults. Methods A multi-site (Concordia University and KITE-Toronto Rehabilitation Institute, University Health Network) single-blinded randomized controlled trial will be conducted whereby participants are randomized to either 12 weeks of at-home computerized executive function training or a wait-list control. Participants will consist of normal-hearing middle-aged adults (45–60 years old) and older adults (65–80 years old), as well as older hearing aid users (65–80 years old, ≥ 6 months hearing aid experience). Separate samples will undergo the same training protocol and the same pre- and post-evaluations of cognition, hearing, and mobility across sites. The primary dual-task outcome measures will involve either static balance (KITE site) or treadmill walking (Concordia site) with a secondary auditory-cognitive task. Dual-task performance will be assessed in an immersive virtual reality environment in KITE’s StreetLab and brain activity will be measured using functional near infrared spectroscopy at Concordia’s PERFORM Centre. Discussion This research will establish the efficacy of an at-home cognitive training program on complex auditory and motor functioning under laboratory and simulated real-world conditions. This will contribute to rehabilitation strategies in order to mitigate or prevent physical and cognitive decline in older adults with hearing loss. Trial registration Identifier: NCT05418998. https://clinicaltrials.gov/ct2/show/NCT05418998

We recently developed a series of nalfurafine analogs (TK10, TK33, and TK35) that may serve as non-addictive candidate analgesics. These compounds are mixed-action agonists at the kappa and delta opioid receptors (KOR and DOR, respectively) and produce antinociception in a mouse warm-water tail-immersion test while failing to produce typical mu opioid receptor (MOR)-mediated side effects. The warm-water tail-immersion test is an assay of pain-stimulated behavior vulnerable to false-positive analgesic-like effects by drugs that produce motor impairment. Accordingly, this study evaluated TK10, TK33, and TK35 in a recently validated assay of pain-related behavioral depression in mice that are less vulnerable to false-positive effects. For comparison, we also evaluated the effects of the MOR agonist/analgesic hydrocodone (positive control), the neurokinin 1 receptor (NK1R) antagonist aprepitant (negative control), nalfurafine as a selective KOR agonist, SNC80 as a selective DOR agonist, and a nalfurafine/SNC80 mixture. Intraperitoneal injection of dilute lactic acid (IP lactic acid) served as a noxious stimulus to depress vertical and horizontal locomotor activity in male and female ICR mice. IP lactic acid-induced locomotor depression was alleviated by hydrocodone but not by aprepitant, nalfurafine, SNC80, the nalfurafine/SNC80 mixture, or the KOR/DOR agonists. These results suggest that caution is warranted in advancing mixed-action KOR/DOR agonists as candidate analgesics.

Chrononutrition is a rapidly evolving field of nutritional epidemiology that addresses the complex relationship between temporal eating patterns, circadian rhythms, and metabolic health, but most prior research has focused on the cardiometabolic consequences of time-restricted feeding and intermittent fasting. The purpose of this topical review is to summarize epidemiological evidence from observational and intervention studies regarding the role of chrononutrition metrics related to eating timing and regularity in cardiometabolic health preservation and cardiovascular disease prevention. Observational studies are limited due to the lack of time-stamped diet data in most population-based studies. Findings from cohort studies generally indicate that breakfast skipping or the later timing of the first eating occasion, a later lunch and dinner, and a greater proportion of caloric intake consumed in the evening are associated with adverse cardiometabolic outcomes, including higher risk for coronary heart disease, hypertension, type 2 diabetes, obesity, dyslipidemia, and systemic inflammation. Randomized controlled trials are also limited, as most in the field of chrononutrition focus on the cardiometabolic consequences of time-restricted feeding. Overall, interventions that shift eating timing patterns to earlier in the day and that restrict evening caloric intake tend to have protective effects on cardiometabolic health, but small sample sizes and short follow-up are notable limitations. Innovation in dietary assessment approaches, to develop low-cost validated tools with acceptable participant burden that reliably capture chrononutrition metrics, is needed for advancing observational evidence. Culturally responsive pragmatic intervention studies with sufficiently large and representative samples are needed to understand the impact of fixed and earlier eating timing schedules on cardiometabolic health. Additional research is warranted to understand the modifiable determinants of temporal eating patterns, to investigate the role of chrononutrition in the context of other dimensions of diet (quantity, quality, and food and nutrition security) in achieving cardiometabolic health equity, and to elucidate underlying physiological mechanisms.

Throughout the COVID-19 pandemic, scenario modeling played a crucial role in shaping the decision-making process of public health policies. Unlike forecasts, scenario projections rely on specific assumptions about the future that consider different plausible states-of-the-world that may or may not be realized and that depend on policy interventions, unpredictable changes in the epidemic outlook, etc. As a consequence, long-term scenario projections require different evaluation criteria than the ones used for traditional short-term epidemic forecasts. Here, we propose a novel ensemble procedure for assessing pandemic scenario projections using the results of the Scenario Modeling Hub (SMH) for COVID-19 in the United States (US). By defining a “scenario ensemble” for each model and the ensemble of models, termed “Ensemble2”, we provide a synthesis of potential epidemic outcomes, which we use to assess projections’ performance, bypassing the identification of the most plausible scenario. We find that overall the Ensemble2 models are well-calibrated and provide better performance than the scenario ensemble of individual models. The ensemble procedure accounts for the full range of plausible outcomes and highlights the importance of scenario design and effective communication. The scenario ensembling approach can be extended to any scenario design strategy, with potential refinements including weighting scenarios and allowing the ensembling process to evolve over time.

Abstract The seismic potential of the Lesser Antilles subduction zone is poorly known and highly debated. Only two damaging earthquakes have been reported in the historical period, in 1839 and 1843, but their sources and magnitude are still uncertain. Global Navigation Satellite Systems and coral data contradict each other, and no conclusion has been reached on the coupling ratio of the plate interface. Given the threat posed by the possible occurrence of a large megathrust earthquake, it is crucial to gain information on prehistorical events. We present the results of a submarine paleoseismological study that covers an exceptional ∼120 Kyr‐long period. We studied the sediments sampled in six up to 26 m‐long piston cores collected in deep fore‐arc basins located over the epicentral region of the 1843 earthquake. Using a multiproxy approach combining geophysical, geochemical, and sedimentological analysis, biostratigraphy and radiocarbon dating, we identified, characterized, and dated numerous event deposits that we then correlated with the sampled basins over an up to 160 km‐long area. We show that at least 33 earthquakes likely triggered these sediment remobilizations in the last 120 Kyr. Four of these events promoted exceptional deposits of turbidites + homogenites. From peak ground acceleration calculated for potential earthquakes occurring on various faults, and the absence of deposits linked to the historical earthquakes, we propose that the sources are likely megathrust earthquakes. Over the last 60 Kyr, we inferred at least three 15–25 Kyr‐long seismic cycles in which the recurrence times of earthquakes shortens from ∼5 to ∼2 Kyr.